Prolonged survival of mice with Pseudomonas aeruginosa-induced sepsis by rIL-12 modulation of IL-10 and interferon-gamma

Interleukin-12 (IL-12) is thought to play an important role as a modulator of levels of IL-10 and interferon-gamma (IFN-gamma), To address the therape utic effects of rlL-12 in an endogenous sepsis model in mice, which closely mimics the pathophysiology of septicaemia in man, the effects of rIL-12 on the levels of cytokines such as IL-10 and IFN-gamma, and on the survival o f septic mice infected with Pseudomonas aeruginosa PAO1 were examined. Firs t, in the endogenous sepsis model, the serum levels of IFN-gamma and IL-10 remained normal until days 8 and 10, respectively, when significant rises w ere seen, On day 11, levels of IFN-gamma returned to normal, but levels of IL-10 remained high, Interestingly, the IL-10 serum level reached a maximum 2 days later than the IFN-gamma serum level. In the light of these results , septic mice were given 0.01 mu g of rIL-12 by intraperitoneal injection a nd the serum levels of endogenous cytokines and the survival times were exa mined. Mire treated with rIL-12 on days 5, 6 and 7 after infection survived significantly longer than control septic mice treated with saline only, Tr eatment with rlL-12 also led to a significant increase of the serum IFN-gam ma level and a decrease of the serum IL-10 level on day 11. These results s uggest that rIL-12 exerts therapeutic activity against endogenous sepsis ca used by P. aeruginosa by stimulating proinflammatory responses and attenuat ing anti-inflammatory responses.